Alkhumra virus: Infectious substances pathogen safety data sheet

Section I – Infectious agent

Name

Alkhumra virus

Agent type

Virus

Taxonomy

Family

Flaviviridae

Genus

Flavivirus

Species

Kyasanur Forest disease virus

Subspecies/strain/clonal isolate

Alkhumra virus

Synonym or cross-reference

Alkhumra virus (ALKV), Alkhumra hemorrhagic fever virus ^{Footnote 1Footnote 2}, Alkhurma' virus ^{Footnote 3Footnote 4}.

Characteristics

Brief description

ALKV is closely related to Kyasanur Forest disease virus ^{Footnote 1Footnote 2}. ALKV is a single-stranded, positive-sense RNA virus. Its genome is approximately 10.5 kb in length ^{Footnote 1}. ALKV has icosahedral symmetry, is surrounded by a lipid envelope, and measures approximately 40 nm in diameter ^{Footnote 5}.

Section II – Hazard identification

Pathogenicity and toxicity

ALKV is the causative agent of Alkhumra hemorrhagic fever^{Footnote 6Footnote 7}. ALKV infections can be subclinical in some individuals^{Footnote 8}. Symptomatic individuals may experience influenza-like symptoms including fever (96-100%), malaise (59-86%), anorexia (62%), or nausea (60%)^{Footnote 9Footnote 10}. Hemorrhagic manifestations have been reported in 26-55% of patients^{Footnote 9}. Neurological manifestations are less common and include confusion (3-25%), hallucination (4.3%), neck rigidity (1-9%), and convulsion (2-5%)^{Footnote 9Footnote 11}. Disease is biphasic in 3% of symptomatic cases^{Footnote 7}. In these cases, the initial fever persists for 9 to 10 days, followed by a symptom-free period for 2 to 3 days, and a second febrile period for 2 days^{Footnote 7}. Complications including encephalitis have been reported in 12-20% of cases^{Footnote 7Footnote 9}. Overall case fatality rate is approximately 1%^{Footnote 7}, while one outbreak had a mortality rate of 25%^{Footnote 6}.

Epidemiology

ALKV is endemic in Saudi Arabia, since being discovered in 1995, with outbreaks occurring sporadically^{Footnote 7Footnote 10Footnote 12}. Since 2009, approximately 38-93 new cases of Alkhumra hemorrhagic fever are reported in Saudi Arabia every year^{Footnote 10Footnote 11}. Recently travel-related cases, and cases in the surrounding geographic areas have become more prevalent^{Footnote 1Footnote 13}.

Predisposing factors include individuals who handle, or work closely with, raw meat or blood from infected animals. This includes abattoir workers, butchers, and shepherds^{Footnote 12Footnote 14}.

Host range

Natural host(s)

Humans, sheep^{Footnote 15}, camels^{Footnote 1}, goats^{Footnote 11}.

Other host(s)

Mice have been experimentally infected with ALKV^{Footnote 16}.

Infectious dose

Unknown.

Incubation period

Approximately 3 to 8 days^{Footnote 6}.

Communicability

No evidence of human-to-human transmission. ALKV can be transmitted via bites from infected ticks and direct contact with blood or raw meat from infected animals^{Footnote 7Footnote 12Footnote 15}. Although other flaviviruses can be transmitted to humans via consumption of raw milk products^{Footnote 17Footnote 18}, there is currently insufficient evidence to support this transmission pathway for ALKV^{Footnote 8Footnote 19}.

Section III – Dissemination

Reservoir

Potential reservoirs include goats, sheep, and camels^{Footnote 20}.

Zoonosis

ALKV can be transmitted to humans from infected livestock via direct contact with blood or raw meat from infected animals^{Footnote 12Footnote 15}.

Vectors

ALKV is transmitted to mammalian hosts via tick bites. ALKV has been found in soft tick Ornithodoros savignyi^{Footnote 21}, and hard ticks Hyalomma dromedarii and Amblyomma lepidum^{Footnote 19Footnote 22}.

Section IV – Stability and viability

Drug susceptibility/resistance

An adenosine analog (NITD008), 6-Azauridine, 2'-C-methylcytidine, and interferon alpha 2a inhibited ALKV replication in vitro^{Footnote 23Footnote 24}. Perylenyltriazoles, an aglycon analogue of the antibiotic teicoplanin (LCTA-949), and Arbidol (Umifenovir), a broad-spectrum antiviral drug approved in China and Russia for influenza treatment, showed antiviral activity against other flaviviruses in vitro^{Footnote 25Footnote 26Footnote 27}.

Susceptibility to disinfectants

Ethanol (70%) effectively inactivates ALKV^{Footnote 1}. Other members of the Flavivirus genus are inactivated by iodine-based disinfectants (1%), hypochlorite (1%), paraformaldehyde, and glutaraldehyde (2%)^{Footnote 28Footnote 29}.

Physical inactivation

ALKV is inactivated by heat treatment at 60 °C for 3 minutes and 56 °C for 30 minutes^{Footnote 30}. Flaviviruses can be inactivated by UV radiation and extreme pH, (pH ≥ 9)^{Footnote 28Footnote 29}.

Survival outside host

No literature currently provides information on survival of ALKV outside host. Other tick-borne flaviviruses are stable in milk for 72 hours at refrigeration temperature but are not detectable after 48 hours at room temperature^{Footnote 31}.

Section V – First aid/medical

Surveillance

Diagnosis is accomplished through the monitoring of clinical symptoms. ALKV can be detected in blood using reverse transcriptase PCR^{Footnote 8Footnote 32}. ELISA can be used to detect ALKV antibodies in blood, but cross-reaction with other flaviviruses (e.g., dengue, yellow fever, West Nile) can be problematic^{Footnote 8Footnote 14}.

Note: The specific recommendations for surveillance in the laboratory should come from the medical surveillance program, which is based on a local risk assessment of the pathogens and activities being undertaken, as well as an overarching risk assessment of the biosafety program as a whole. More information on medical surveillance is available in the Canadian Biosafety Handbook (CBH).

First aid/treatment

There is no available antiviral treatment for Alkhumra hemorrhagic fever; treatment includes supportive care to manage symptoms^{Footnote 14Footnote 28}.

Note: The specific recommendations for first aid/treatment in the laboratory should come from the post-exposure response plan, which is developed as part of the medical surveillance program. More information on the post-exposure response plan can be found in the CBH.

Immunization

No vaccine is currently available.

Note: More information on the medical surveillance program can be found in the CBH, and by consulting the Canadian Immunization Guide.

Prophylaxis

None.

Note: More information on prophylaxis as part of the medical surveillance program can be found in the CBH.

Section VI – Laboratory hazard

Laboratory-acquired infections

None have been reported to date.

Note: Please consult the Canadian Biosafety Standard (CBS) and CBH for additional details on requirements for reporting exposure incidents. A Canadian biosafety guideline describing notification and reporting procedures is also available.

Sources/specimens

Blood/serum and biopsy specimens can be sources of ALKV.

Primary hazards

Exposure of mucous membranes or wounded skin to infectious material, and bites/scratches of an infected animal are the primary hazards associated with ALKV exposure.

Special hazards

None.

Section VII – Exposure controls/personal protection

Risk group classification

Alkhumra virus is a Risk Group (RG) 4 human pathogen and a RG 4 animal pathogen^{Footnote 33Footnote 34}.

Containment requirements

Containment Level 4 facilities, equipment, and operational practices outlined in the CBS for work involving infectious or potentially infectious materials, animals, or cultures.

Protective clothing

The applicable Containment Level 4 requirements for personal protective equipment and clothing outlined in the CBS to be followed. The use of a positive-pressure suit or use of a Class III biological safety cabinet (BSC) line is required for all work with RG4 pathogens.

Note: A local risk assessment will identify the appropriate hand, foot, head, body, eye/face, and respiratory protection, and the personal protective equipment requirements for the containment zone must be documented.

Other precautions

All activities involving open vessels of infectious material are to be performed in a certified biological safety cabinet (BSC) or other appropriate primary containment device. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are unloaded in a biological safety cabinet. The integrity of positive pressure suits must be routinely checked for leaks. The use of needles, syringes, and other sharp objects to be strictly limited. Open wounds, cuts, scratches, and grazes are to be covered with waterproof dressings. Additional precautions must be considered with work involving animal activities.

Section VIII – Handling and storage

Spills

The spill area to be evacuated and secured. Aerosols must be allowed to settle for a minimum of 30 minutes. Spills of potentially contaminated material to be covered with absorbent paper-based material (e.g., paper towels), liberally covered with an effective disinfectant (e.g., 1% sodium hypochlorite), and left to soak for an appropriate amount of time (e.g., 10 minutes) before being wiped up. Following the removal of the initial material, the disinfection process is to be repeated. Individuals performing this task must wear PPE, including particulate respirators (e.g., N95 or higher). Disposable gloves, impermeable gowns and protective eye wear are to be removed immediately after completion of the process, placed in an autoclave bag, and decontaminated prior to disposal (CBH).

Disposal

All materials/substances that have come in contact with the infectious agent must be completely decontaminated before they are removed from the containment zone. This can be achieved by using decontamination technologies and processes that have been demonstrated to be effective against the infectious material, such as chemical disinfectants, autoclaving, irradiation, incineration, an effluent treatment system, or gaseous decontamination (CBH).

Storage

The applicable Containment Level 4 requirements for storage outlined in the CBS are to be followed. Pathogens, toxins, and other regulated materials to be stored inside the containment zone.
Inventory of Risk Group 4 (RG4) pathogens in long-term storage to be maintained and to include:

• specific identification of the pathogens, toxins, and other regulated materials; and
• a means to allow for the detection of a missing or stolen sample in a timely manner.

Section IX – Regulatory and other information

Canadian regulatory information

Controlled activities with ALKV require a Human Pathogens and Toxins Licence, issued by the Public Health Agency of Canada. ALKV is a non-indigenous animal pathogen in Canada; therefore, importation of ALKV requires an import permit, issued by the Canadian Food Inspection Agency.

The following is a non-exhaustive list of applicable designations, regulation, or legislation:

• Human Pathogen and Toxins Act and Human Pathogens and Toxins Regulations
• Health of Animals Act and Health of Animals Regulations
• Transportation of Dangerous Goods Regulations

Last file update

October, 2019

Prepared by

Centre for Biosecurity, Public Health Agency of Canada.

Disclaimer

The scientific information, opinions, and recommendations contained in this Pathogen Safety Data Sheet have been developed based on or compiled from trusted sources available at the time of publication. Newly discovered hazards are frequent and this information may not be completely up to date. The Government of Canada accepts no responsibility for the accuracy, sufficiency, or reliability or for any loss or injury resulting from the use of the information.

Persons in Canada are responsible for complying with the relevant laws, including regulations, guidelines and standards applicable to the import, transport, and use of pathogens in Canada set by relevant regulatory authorities, including the Public Health Agency of Canada, Health Canada, Canadian Food Inspection Agency, Environment and Climate Change Canada, and Transport Canada. The risk classification and related regulatory requirements referenced in this Pathogen Safety Data Sheet, such as those found in the Canadian Biosafety Standard, may be incomplete and are specific to the Canadian context. Other jurisdictions will have their own requirements.

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